Skip to Accessibility Tools Skip to Content Skip to Footer

Targeted Therapies

Cancer cells are different from normal cells. Many cancer cells have mutations that cause them to grow and survive when normal cells would not. Uncontrolled cell growth is what leads to cancer.

Targeted therapies aim at the features that make cancer cells different. They are some of the newest medications for skin cancer.

What is a cell?

Cells are the building blocks for your body.1,2 They do your body’s work. They provide structure. They turn nutrients into energy. They perform specialized jobs.

A membrane (outer lining) surrounds the cell. Inside the cell are many different organelles (special structures) that do the cell’s work. The nucleus is the cell’s command center. The nucleus contains the DNA. DNA has the instructions (genes) for making different proteins.

Figure 1. Cell structure

A cut away of a skin cell showing each different part.

How does normal cell signaling work?

There are receptors within the cell membrane. Part of the receptor may stick out of the cell (“extracellular domain”). Part of the receptor may stick into the cell (“intracellular domain”).

Receptors receive chemical signals from outside the cell. Examples of chemical signals are hormones, growth factors, or cytokines. The chemical signal binds with (plugs into) the receptor. Binding activates (turns on) the receptor. The activated receptor changes within the cell. Proteins may move toward the receptor and activate other proteins.

These proteins pass signals from one to the other, like a game of telephone. Eventually, the signal gets to the nucleus. In the nucleus, the instructions for building a protein are copied from the DNA. Other parts of the cell assemble the protein.

In normal cells, there are “on” and “off” switches for these chains of events. A pathway only becomes active as needed.

Cancer develops when there are harmful changes in DNA. These harmful changes are called mutations. For example, a mutation can lead to a receptor that stays active all the time, instead of turning “on” and “off” as appropriate.

Figure 2. Basic cell signaling

Showing how cell signaling interact with different proteins which change the DNA transcription

How is targeted therapy used to treat skin cancer?

Targeted therapies are available to treat some types of skin cancers. Specifically, targeted therapies treat:

What targeted therapies treat advanced melanoma with BRAF mutation?

Targeted therapies have improved outcomes for people with advanced melanoma. Advanced melanoma is cancer that:

  • Has spread to distant parts of the body (metastasized) or
  • Cannot be treated with surgery (unresectable)

Up to 50% of melanomas have BRAF mutations.3 BRAF is a protein in the MAPK (or ERK) pathway, which is involved in the cell’s growth. BRAF mutations can cause cancer cells to grow uncontrollably. Today, there are several medications for advanced melanoma with BRAF mutation, including:

These medications have slightly different uses. All of the BRAF inhibitors treat melanoma with the BRAF V600E mutation.4-6 V600E is the most common type of BRAF mutation in melanoma. Tafinlar also is approved for BRAF V600K mutation.5 BRAF inhibitors improve response rates, progression-free survival, and overall survival.6,7 They have somewhat different side effects.

MEK is protein that that is further along the MAPK pathway. Medications that target MEK include:

Taken by themselves, MEK inhibitors do not work for many patients.7 That is why these medications are typically paired with a BRAF inhibitor:

  • Tafinlar/Mekinist
  • Zelboraf/Cotellic
  • Braftovi/Mektovi

What targeted therapies treat advanced melanoma with c-KIT mutation?

National cancer guidelines suggest Gleevec® (imatinib) as one option for advanced melanoma with c-KIT mutation.7 This use of Gleevec is not approved by the Food and Drug Administration.8 Nevertheless, it is an option when other treatments are not working.7

The c-KIT receptor kick starts several different signaling pathways. Up to 20% of acral or mucosal melanomas have c-KIT mutations.9 These are types of melanoma that are not related to sun exposure.

A new c-KIT inhibitor named Tasigna® (nilotinib) is being researched. It is approved to treat certain forms of blood cancer but not melanoma.

What targeted therapies treat advanced basal cell carcinoma?

Surgery is more effective than targeted therapy for BCC. Targeted therapies have serious risks and side effects. Therefore, medication is only used when surgery or radiation are no longer options.10

Two medications called SMO inhibitors treat advanced BCC:

SMO is short for “Smoothened.” SMO is a receptor in a cellular signaling pathway called the Hedgehog pathway. About 40% of BCC have mutations that cause an overactive Hedgehog pathway.11

The approved uses for these two medications are slightly different. Erivedge treats metastatic and locally advanced BCC.12 Odomzo treats locally advanced BCC only.13

Both medications carry a serious risk of birth defects and stillbirth. Other common side effects of these medications include muscle spasms, hair loss, and taste changes. The label for Odomzo includes a warning about rare but serious muscle injury.13

Written by: Sarah O'Brien and Emily Downward | Last reviewed: December 2019.
  1. Genetics Home Reference. What is a cell? Accessed April 5, 2017 at:
  2. Winslow T. Cell structure – parts of a cell (illustration). 2014. National Cancer Institute Visuals Online. Accessed April 5, 2017 at:
  3. Lovly C, Pao W, Sosman J. 2016. Molecular profiling of melanoma. My Cancer Genome (Updated January 26).
  4. Zelboraf® [prescribing information]. South San Francisco, CA: Genentech; September 2016.
  5. Tafinlar® [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; June 2016.
  6. Braftovi prescribing information. Available at Accessed 12/5/18.
  7. NCCN Clinical Practice Guidelines in Oncology. Melanoma. Version 1.2017. Published November 10, 2016.
  8. Gleevec® [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; September 2016
  9. Lovly C, Sosman J, Pao W. 2015. KIT in melanoma. My Cancer Genome (Updated June 18).
  10. NCCN Clinical Practice Guidelines in Oncology. Basal cell skin cancer. Version 1.2017. Published October 3, 2016.
  11. My Cancer Genome. Hedgehog signaling. Accessed January 18, 2016 at:
  12. Erivedge® [prescribing information]. South San Francisco, CA: Genentech USA, Inc; November 2016.
  13. Odomzo® [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; July 2015.